Clinical, epidemiological and chronobiological studies on the relationship between blood pressure and mineral intake have been on-going for the past thirty years. They can be divided into five groups. 1) Clinical studies on salt sensitivity in patients with idiopathic hypertension. 2) Chronobiological studies of blood pressure (BP) fluctuation and urinary electrolyte excretion in relation to BP regulation. These include the Fukuoka-Minnesota collaborative chronoepidemiological study, studies on the circadian rhythns of urinary electrolyte excretion during total parenteral nutrition, and the reapportionment of salt intake in relation to circadian blood pressure patterns. 3) The estimation of the 24-h urinary sodium and potassium excretion from spot-urine specimens. 4) Comparative epidemiological studies on the genesis of hypertension in Nepal. 5) The effects of high-potassium, high-magnesium or high-fiber intake on blood pressure and the metabolism of lipids and carbo-hydrates in man. A larger proportion of te population are expected to suffer from either mild or borderline hypertension in the future. Non-pharmacological treatment of this condition by regulating the dietary intake of minerals such as sodium, potassium, magnesium and calcium, is now considered to be of increasing importance for the treatment of this condition.
Regulatory mechanisms of hepatic protein metabolism and gene expression mediated by amino acids and vitamin B6 were investigated. 1) Rats were nourished by total parenteral nutrition, and the effects of variations in the amino acid supply on the rates of hepatic protein synthesis and degradation were investigated. Amino acids decreased the rate of degradation whilst the rate of synthesis was relatively unaffected. Protein degradation, therefore, predominates the regulation of liver protein mass. 2) Studies on cystathionase and aspartate aminotransferase (AspAT) in the liver of vitamin B6-deficient rats showed that their rates of synthesis and degradation were both increased. The enhanced degradation was caused by different susceptibilities of apo- and holo-enzymes to lysosomal proteolysis. 3) Pyridoxal phosphate (PLP) was found to modulate AspAT gene expression by preventing the glucocorticoid receptor from binding to glucocorticoid-responsive elements. PLP also modulated albumin gene expression by inactivat ng the DNA-binding activity of tissue-specific transcriptional factors such as HNF-1 and C/EBP. 4) Amino acid vinfusion increased the albumin mRNA level and decreased the PLP concentration. The decrease in PLP concentration would prevent the inactivation of tissue-specific transcription factors and enhance albumin gene expression. The present study sheds new light on the physiological role of PLP as a mediator of gene regulation in protein/amino acid nutrition.